The Association of Environmental Variables with Intelligence and Well-Being in Copy Number Variation (CNV) Carriers

Copy Number Variants (CNVs) are structural genomic alterations that have been linked to cognitive deficits and susceptibility to neurodevelopmental and psychiatric disorders, with their impact often shaped by interactions with environmental factors such as socioeconomic status (SES), stress, and lifestyle. This study leverages UK Biobank data to explore how these interactions influence fluid intelligence and well-being, two key indicators of cognitive and psychosocial functioning, in CNV carriers, aiming to identify factors for personalized interventions. We investigated interactions between common pathological CNVs - 1q21.1 distal, 15q11.2, 15q13.3 BP4-BP5, 16p11.2 proximal and distal, and 22q11.2 proximal and distal - and key environmental variables, including SES, stress, and lifestyle, on fluid intelligence and well-being. Using ANOVA models with interaction terms, we examined how interactions between CNV status and environmental factors impact cognition and well-being. SES variables interacted with CNV status in distinct ways. While non-carriers exhibited the expected association of higher fluid intelligence with increasing SES, 16p11.2 distal deletion carriers in the moderate SES group had lower fluid intelligence than both non-carriers in the same SES group and carriers with low SES. Stress-related interactions varied by CNV type: in 16p11.2 proximal duplication carriers, higher adulthood stress was significantly associated with increased fluid intelligence. Furthermore, 15q11.2 deletion carriers exhibited significantly lower fluid intelligence in the moderately healthy lifestyle group compared to all non-carrier groups (p < 0.01). By revealing how environmental factors interact with CNV status, this study identifies potential targets for personalized interventions aimed at supporting cognitive and emotional resilience in genetically at-risk individuals.